Linked Life Data

19151754

Source:http://linkedlifedata.com/resource/pubmed/id/19151754

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2009-3-5
pubmed:abstractText
E-cadherin (cadh), a member of a family of integral membrane glycoproteins that represent the major component of adherens junctions (AJs), mediates cell-cell adhesion through the calcium-dependent homophilic interaction of its extracellular domain. Metastatic human carcinomas frequently lose E-cadh expression, whereas epithelial ovarian cancer (EOCs) maintain properties characteristic of Müllerian epithelium during tumor progression, including E-cadh expression. Here, we examined the potential role of cell-cell contacts in EOCs through E-cadh homophilic interactions in PI3K/AKT activation whose altered signaling has been implicated in EOC pathogenesis. We show that E-cadh is predominantly expressed at cell-cell contacts and its functionality is necessary and sufficient for the activation of the PI3K/AKT pathway. E-cadh knockdown and phosphoinositide-3-kinase (PI3K) inhibition complement each other in impairing cell-cycle progression and proliferation of ovarian carcinoma cells. E-cadh is stably bound to the PI3K complex, and the de novo formation of E-cadh/beta-catenin complexes following calcium deprivation and subsequent calcium restoration recruits the PI3K p85 subunit to the site of the cell-cell contacts. The finding that E-cadh-mediated AJ formation contributes to PI3K/AKT activation in EOC cells by a mechanism that appears to be restricted to these cells provides the underpinning for therapeutic strategies that exploit PI3K inhibition to halt EOCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1206-17
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
E-cadherin directly contributes to PI3K/AKT activation by engaging the PI3K-p85 regulatory subunit to adherens junctions of ovarian carcinoma cells.
pubmed:affiliation
Unit of Molecular Therapies, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't